Leu-enkephalin content in rat brain during prolonged treatment with imipramine or amitriptyline.

Male Wistar rats were treated with imipramine /IMI/ /2 or 10 mg/kg, p.o./ or amitriptyline /AMI/ 10 mg/kg, p.o./ by drinking water. Each drug was given once or over periods of 1, 3, 4, 6 and 9 months. Leu-enkephalin /LENK/ content was measured by radioimmunoassay in the striatum, hypothalamus and brain perfusates after different periods of the treatment with antidepressants. A single 10 mg/kg dose of IMI increased the level of LENK in the striatum and decreased it in the hypothalamus. Six months after IMI treatment the level of LENK in the striatum was decreased after a 2 mg/kg dose and increased after 10 mg/kg; in the hypothalamus a dose-dependent increase of LENK content was observed. In brain perfusates the level of LENK was decreased 3 months after IMI treatment, but highly increased after a 9-month administration. This indicates that during prolonged treatment with imipramine the central enkephalinergic activity is dynamically changed and can affect the psychopharmacological effects of IMI. After the prolonged treatment with AMI a decrease of LENK level in the striatum was observed only after 4 months of the drug administration, and no changes were seen in the hypothalamus. It is suggested that both antidepressants studied have different action on the central enkephalinergic system.